Pim-1 kinase protects the liver from ischemia reperfusion injury by regulating dynamics-related protein 1.

Hepatic ischemia-reperfusion (IR) injury significantly impacts liver transplantation success, yet current treatments remain inadequate. This study explores the role of Proto-oncogene serine/threonine-protein kinase (Pim-1) in liver IR, an area previously unexplored. Utilizing a mouse liver IR in vivo model and a MIHA cell hypoxia-reoxygenation in vitro model, we observed that Pim-1 expression increases following IR, inversely correlating with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Increased Pim-1 expression stabilizes mitochondrial membranes by modifying Drp1 phosphorylation, reducing mitochondrial fission and apoptosis, thereby mitigating liver damage. Additionally, we discovered that elevated Pim-1 expression is dependent on the trimethylation of histone H3 lysine 9 during liver IR. These findings underscore the importance and potential clinical application of targeting Pim-1 in treating hepatic IR, presenting a novel therapeutic avenue.

Marginal donor liver versus standard donor liver: A single-center observational study.

BACKGROUND: The effectiveness and safety of marginal donor livers remain controversial. This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation (LT). METHODS: This study included 199 liver donors (including 16 split donors) and 206 liver recipients from January 1, 2018 to January 27, 2020, with case follow-up until July 31, 2021. Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers. Indices of liver and kidney functions, complications, and survival curves of the two groups were compared. RESULTS: Compared with the standard donor group, the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation (P < 0.05); there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels after LT (all P > 0.05); there was no significant difference in the incidence of complications after LT (P > 0.05); there was also no significant difference in the survival curve (P = 0.335). CONCLUSIONS: There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups. The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.

Transient elastography for assessment of fibrosis and steatosis of liver grafts from brain-death donors.

BACKGROUND: An objective and accurate evaluation of liver grafts is required to improve the prognosis of liver transplant recipients and to increase the number of available liver grafts. AIM: To compare outcomes using FibroScan with that of pathology in liver grafts from brain-dead donors (DBD). METHODS: Liver grafts from 52 DBD were examined using ultrasound (US), FibroScan before liver transplantation (LT). Blood tested before LT and a biopsy was performed pre- or intra-operation to determine pathology. The diagnostic accuracy of the FibroScan results was compared with the pathology results, which is the gold standard for evaluating liver grafts. The donors enrolled were grouped by the stage of liver fibrosis (F0-F4) and steatosis (S0-S3), based on Kleiner's scoring system of nonalcoholic fatty liver disease, respectively. RESULTS: The liver stiffness (LS) value in group F1 was significantly increased compared with group F0 (8.74±1.32kPa and 5.93±1.64kPa, respectively, P<0.01). The LS value had a significant positive correlation with the liver graft fibrosis stage (r=0.73, P<0.01). The area under receiver operating characteristic curves (AUROC) for F1 stage fibrosis was 0.93 (P<0.01). Significant differences in the controlled attenuation parameter (CAP) were found among groups S0, S1, and S2 (173.30±38.36dB/m, 230.29±23.27dB/m, 250.00±57.01dB/m, respectively; F=12.41, P<0.01). The CAP was associated with the liver graft steatosis stage (r=0.64, P<0.01). The AUROC for S1 and S2 stage steatosis in liver grafts was 0.89 (P=0.002) and 0.83 (P=0.007), respectively. CONCLUSIONS: Transient elastography quantifies fibrosis and steatosis in liver grafts from 52 DBD with a high diagnostic accuracy and provides further imaging evidence for use in assessing liver grafts.